Biomedical subjects

Wen Tan

Publications and source records attributed to Wen Tan.

At least 37 records · Page 2Linked to original sources

PubMed2005

[Polymorphisms in nucleotide excision repair genes XPC and XPD and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer].

OBJECTIVE: Nucleotide excision repair has been shown to have great impact on the sensitivity of tumors to platinum-based chemotherapy. This study was to examine the association between genetic polymorphisms in XPC and XPD, two important components in nucleotide excision repair system, and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer. METHODS: Patients (n = 151) treated with platinum-based chemotherapy were genotyped for the AT dinucleotide insertion or deletion in intron 9 of XPC or Lys751Gln polymorphism in XPD. Clinical response to chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model and adjusted for sex, age, clinical stage, and regime of chemotherapy. RESULTS: The overall response rate to the chemotherapy (CR + PR) was 35.1%, with 1 CR, 52 PR, 75 SD, and 23 PD. It was found that patients with the XPC LL genotype had significantly higher response rate than patients with the XPC SS genotype (adjusted OR = 3.19, 95% CI = 1.11 - 9.17; P = 0.031). However, no association was found between the XPD Lys751Gln polymorphism and response to the chemotherapy. In addition, these two polymorphisms seemed to have synergic effect, with the OR being 2.90 (95% CI = 1.07 - 7.86) for patients carrying the XPC LL and XPD Lys/Lys genotypes compared with those carrying the XPC SS or SL and XPD Lys/Lys genotypes. CONCLUSION: These results suggest that genetic polymorphisms in nucleotide excision repair might be associated with clinical response to platinum-based chemotherapy.

Adult↗

PubMed2005

Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population.

p73, a structural and functional homologue of p53, shares some p53-like tumor suppressor activity but also possesses oncogenic activity. Therefore, p73 plays an important role in modulating cell-cycle control and apoptosis. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. To test the hypothesis that these 2 common variants play a role in lung cancer susceptibility, we conducted a case-control study of 425 lung cancer patients and 588 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population. The results showed that these 2 polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less common in the cases (0.225) than in the controls (0.287) (p = 0.0018), suggesting that this AT haplotype was protective against lung cancer. Compared to the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI: 0.26-0.80 and OR: 0.70, 95% CI: 0.53-0.92, respectively). These results suggest that this p73 dinucleotide polymorphism may have a role in lung cancer susceptibility in our study population. Further studies are needed to elucidate potential functional relevance of the p73 AT variant allele.

Aged↗

PubMed2005

Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status.

Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair. The impaired TS expression has been shown to be related to 28 bp tandem repeats and a G-->C SNP in the 5'-UTR of TS. Folate deficiency has been demonstrated to play a role in gastroesophageal carcinogenesis. This case-control study was to examine the hypothesis that the TS polymorphisms, alone or in combination with serum folate status, may confer susceptibility of the hosts to gastroesophageal cancer. We analyzed TS genotype and serum folate concentration in 324 patients with esophageal squamous cell carcinoma (ESCC), 231 patients with gastric cardia adenocarcinoma (GCA) and 492 controls. It was found that compared with the normal expression TS genotype, the low expression TS genotype alone was significantly associated with increased risk of ESCC [adjusted odds ratio (OR) 1.47; 95% confidence interval (CI) 1.03-2.10] but not GCA (OR=0.98, 95% CI=0.68-1.40). More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Among subjects with low serum folate concentration (<3 ng/ml), the ORs of ESCC and GCA for the low expression genotype were 22.63 (95% CI=10.44-49.05) and 4.08 (95% CI=1.94-8.59), which were greater than respective 9.97 (95% CI=5.67-17.53) and 1.88 (95% CI=1.18-3.24) for the normal expression genotype (P=0.002 and 0.029). These results suggest an important role for folate deficiency and impaired TS activity in the etiology of ESCC and GCA.

Adult↗

PubMed2005

Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung cancer susceptibility.

Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer initiation and progression. Our previous studies revealed that the -1306C-->T and -735C-->T polymorphisms in MMP2 promoter significantly influence transcriptional activity and their genotypes and haplotypes are associated with susceptibility to several cancers. This case-control study examined the contribution of these two polymorphisms to the risk of developing lung cancer. MMP2 genotypes and haplotypes were determined in 770 cases and 777 controls and the associations with risk of lung cancer were estimated by logistic regression. We observed a 2-fold [odds ratio (OR), 2.12; 95% confidence interval (CI), 1.64-2.72] or 1.6-fold (OR, 1.57; 95% CI, 1.27-1.95) excess risk of developing lung cancer for the -1306CC or -735CC genotype carriers compared with non-carriers, respectively. A greater risk of lung cancer was associated with the C(-1306)-C(-735) haplotype (OR, 5.01; 95% CI, 2.57-9.78) compared with the T(-1306)-T(-735) haplotype, suggesting a synergic effect of these two polymorphisms. Furthermore, a greater than additive joint effect of the polymorphisms and smoking increased an even higher risk of lung cancer. The OR for smokers with the C(-1306)-C(-735) haplotype was 6.24 (95% CI, 4.51-8.64), which was significantly higher than that (OR, 4.10; 95% CI, 2.89-5.81) of smokers with the T(-1306) or T(-735)-containing haplotypes (P < 0.001). These results are consistent with our previous findings and further support the hypothesis that gain-of-function of MMP2 resulting from genetic polymorphisms plays an important role in human carcinogenesis.

Case-Control Studies↗

PubMed2005

Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer.

Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln have been associated with altered protein function and BER activity. This case-control study examined the contribution of these two polymorphisms, alone and in combination, or in interaction with smoking, to the risk of developing lung cancer. We estimated the risk of lung cancer associated with these polymorphisms in 1,000 cases and 1,000 cancer-free controls using logistic regression models. Subjects having the ADPRT Ala/Ala genotype had an odds ratio (OR) of 1.68 [95% confidence interval (95% CI), 1.27-2.23] compared with those having the Val/Val genotype. A greater than multiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CI) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or =16, 16 to 28, or >28 pack-years were 1.13 (0.79-1.62), 1.35 (0.68-2.70), 2.46 (1.35-4.51) or 17.09 (8.15-35.83), respectively (P trend test < 0.001). Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased risk of lung cancer in a supermultiplicative manner (OR for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, 5.91; 95% CI, 2.09-16.72), although the XRCC1 polymorphism itself was not associated with the risk. In conclusion, the ADPRT Val762Ala polymorphism plays an important role in smoking-related lung cancer and the XRCC1 Arg399Gln polymorphism may serve as a risk modifier.

Aged↗

PubMed2005

Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer.

BACKGROUND & AIMS: Overexpression of cyclooxygenase-2 (COX-2) is implicated in many steps of cancer development. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to identify functional SNPs in the COX-2 promoter and evaluated their effects on the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: Thirty individual DNA samples were sequenced to search for SNPs, and the function of the SNPs was examined by a set of biochemical assays. Genotypes and haplotypes were analyzed in 1026 patients and 1270 controls, and odds ratios and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Three SNPs, -1290A-->G, -1195G-->A, and -765G-->C, were identified; the frequencies of variant alleles were 0.04, 0.51, and 0.02, respectively. The -1195G-->A change creates a c-MYB binding site and displays a higher promoter activity. The -1195A-containing haplotypes had significantly increased luciferase expression and COX-2 messenger RNA levels in esophageal tissues compared with the -1195G-containing counterparts. A case-control analysis showed a 1.72-fold (95% CI, 1.35-2.20) and 2.24-fold (95% CI, 1.59-3.16) excess risk of developing ESCC for the -1195AA or -765CC genotype carriers compared with noncarriers. A greater risk of developing ESCC was observed for A(-1195)-C(-765)-containing haplotypes compared with G(-1195)-G(-765)-containing haplotypes, suggesting an interaction between the -1195G-->A and -765G-->C polymorphisms in the context of haplotype. CONCLUSIONS: These findings indicate that genetic variants in COX-2 may play a role in mediating susceptibility to esophageal cancer.

Adult↗

PubMed2005

Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer.

BACKGROUND & AIMS: Human pancreatic cancer might be associated with folate deficiency and impaired metabolism. We tested this hypothesis by examining the contribution of functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) to risk of cancer. METHODS: DNA from 163 pancreatic cancer patients and 337 control subjects was genotyped for MTHFR (677C > T and 1298A > C) and TS (5'-untranslated region tandem repeat and G/C). Association with risk of pancreatic cancer was estimated by logistic regression. All statistical tests were two-sided. RESULTS: We observed an increased risk of pancreatic cancer associated with the MTHFR 677CT (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.61-4.29; P = .0005) or 677TT (OR, 5.12; 95% CI, 2.94-9.10; P < .0001) genotype compared with the MTHFR CC genotype. An increased risk of pancreatic cancer was also associated with the TS 3Rc/3Rc genotype (OR, 2.19, 95% CI, 1.13-4.31; P = .022) compared with the TS 3Rg/3Rg genotype. Joint effect between MTHFR C677T polymorphism and smoking or drinking increased risk of pancreatic cancer in a super-multiplicative manner. The ORs for smoking, the polymorphism, and both factors combined were 0.70 (95% CI, 0.30-1.63), 2.17 (95% CI, 1.17-4.21), and 3.10 (95% CI, 1.54-6.51), respectively. This joint effect was much stronger in heavy smokers (OR, 6.69; 95% CI, 3.39-13.63; P < .0001). The ORs for drinking, the polymorphism, and both factors combined were 0.98 (95% CI, 0.40-2.30), 2.81 (95% CI, 1.65-4.98), and 4.39 (95% CI, 2.25-8.78), respectively. CONCLUSION: The MTHFR and TS polymorphisms are genetic determinants for developing pancreatic cancer.

Adult↗

PubMed2005

[Association of two genetic polymorphisms in the 5'untranslated region of exon 2 of the p73 gene and risk of lung cancer].

OBJECTIVE: To study the relationship between two potential functional polymorphisms in exon 2 of the p73 gene and the susceptibility of lung cancer. METHODS: Genotypes were determined by polymerase chain reaction-single stand conformation polymorphism (PCR-SSCP) method in 425 histologically-confirmed lung cancer cases and 588 cancer-free controls, frequency-matched by age and sex. RESULTS: The two polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less commonly seen in the cases (0.225) than in the controls (0.287) (P = 0.0018). Compared with the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk [adjusted odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26 - 0.80 and OR = 0.70, 95% CI = 0.53-0.92, respectively]. CONCLUSION: These results suggested that this p73 dinucleotide polymorphism might have had a role to play in the susceptibility of lung cancer.

5' Untranslated Regions↗

PubMed2005

[Association of two exonic genetic polymorphisms in the DNA repair gene XPC with risk of lung cancer in Chinese population].

OBJECTIVE: To explore the relationship between two exonic polymorphisms of DNA repair gene XPC and the susceptibility to lung cancer. METHODS: Genotypes were determined by the primer introduced restriction analysis-PCR(PIRA-PCR) and the PCR-restriction fragment length polymorphism(PCR-RFLP) approaches, respectively, in 320 histologically-confirmed lung cancer cases and 322 age and sex frequency-matched cancer-free controls. RESULTS: Multivariate logistic regression analysis revealed that individuals carrying at least one 499Val variant allele (Ala/Val + Val/Val genotypes) had a significantly increased risk for lung cancer (adjusted OR=1.54; 95%CI: 1.11-2.14), compared with the wild-type genotype (499Ala/Ala). Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR=2.55; 95%CI: 1.45-4.52), compared with those with both wild-genotypes. In addition, a potential super multiplicative gene-environment interaction between Ala499Val genotypes and smoking on lung cancer risk was unveiled. The odds ratios of lung cancer for individuals with both putative risk genotypes were 2.63 (95%CI=1.23-5.62) in nonsmokers and 7.36 (95%CI=3.19-17.0) in smokers, respectively. CONCLUSION: These findings support the hypothesis that these two XPC variants may contribute to the risk of developing lung cancer.

Asian People↗

PubMed2005

[Correlation of polymorphisms of UDP-glucuronosyltransferase 1A7 gene to genetic susceptibility of lung cancer].

BACKGROUND & OBJECTIVE: UDP-glucuronosyltransferase 1A7 (UGT1A7) plays an important role in detoxification through catalyzing combination of glucuronic acid and tobacco carcinogens, including benzo [alpha] pyrene, nitrosamine, and heterocyclic amine PhIP, therefore, inactivates the carcinogens. This study was to examine the correlation of polymorphisms of UGT1A7 gene to genetic susceptibility of lung cancer. METHODS: Polymorphisms of UGT1A7 gene at 12-131 and 208 sites in peripheral lymph cells of 312 patients and 317 age- and sex-matched controls were detected by polymerase chain reaction-denaturized high performance liquid chromatography (PCR-DHPLC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP); the correlation of these polymorphisms to genetic susceptibility of lung cancer was analyzed. RESULTS: Compared with the UGT1A7*1/*1 genotype carriers, the UGT1A7*3/*1 genotype carriers had a 1.80-fold increased risk of lung adenocarcinoma [adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 1.03-3.12], the UGT1A7*3 genotype carriers had a 1.59-fold increased risk of lung adenocarcinoma (adjusted OR, 1.59; 95% CI, 0.96-2.63). The UGT1A7 polymorphisms had no correlation with risk of lung squamous cell carcinoma. CONCLUSION: UGT1A7 gene polymorphisms may increase the genetic susceptibility of lung adenocarcinoma in Chinese.

Adenocarcinoma↗

PubMed2005

[Association between genetic variations in methylenetetrahydrofolate reductase and risk of colorectal cancer in a Chinese population].

OBJECTIVE: To investigate the association between genetic variations in methylenetetrahydrofolate reductase (MTHFR) and the risk of colorectal cancer in a Chinese population. METHODS: One hundred and ninety-eight cases of colorectal cancer and 420 controls were genotyped for detecting MTHFR C677T and A1298C polymorphisms by PCR-RFLP methods. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model. RESULTS: The frequency of the MTHFR C677T allele found among cases was significantly more frequent than that among controls (51.3% to 44.4%, P = 0.02). As compared with the 677CC genotype, the 677TT genotypes had a 67% (95% CI, 1.05 - 2.66) increased risk of colorectal cancers. However, there appeared no any correlations between the genetic variations of MTHFR and the cancer metastasis. CONCLUSION: These findings demonstrated that the genetic variation of MTHFR C677T should be a genetic susceptibility factor for colorectal cancer in a Chinese population.

Asian People↗

PubMed2005

[Correlation of genetic polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer patients to platinum-based chemotherapy].

BACKGROUND & OBJECTIVE: DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. This study was to examine the correlations of polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer (NSCLC) to platinum-based chemotherapy. METHODS: Treatment outcomes of 200 advanced NSCLC patients, treated with platinum-based chemotherapy, were evaluated. XPC-PAT, XPD Lys751Gln (rs1052559), and ERCC1 C8092A (rs1052559) were genotyped by polymerase chain reaction-amplified fragment length polymorphism (PCR-AFLP) or PCR-restrictive fragment length polymorphism (PCR-RFLP) methods in the 200 patients. Unconditional logistic regression model was used to analyze the correlation of genetic polymorphisms to clinical response. RESULTS: The distributions of XPC-PAT genotypes differed significantly between response group (complete response + partial response) and un-response group (stable disease + progressive disease)(P=0.023). The XPC LL genotype carriers had higher response rate than the SS genotype carriers (OR=3.04; 95% CI=1.25-7.41, P= 0.015). The XPD Lys751Gln and ERCC1 C8092A polymorphisms were not found to be associated with platinum-based chemotherapy. However, these 3 genetic polymorphisms in nucleotide excision repair system had interaction in the drug sensitivity (P=0.021). CONCLUSION: The genetic polymorphisms of XPC-PAT, XPD Lys751Gln, and ERCC1 C8092A in nucleotide excision repair system may be associated with sensitivity of NSCLC patients to platinum-based chemotherapy.

Adult↗

PubMed2005

[Association between genetic polymorphisms in methylentetrahydrofolate reductase and risk of lung cancer].

OBJECTIVE: To investigate the association between methylentetrahydrofolate reductase (MTHFR) polymorphisms and risk of lung cancer. METHODS: Totally 505 cases with lung cancer and 500 frequency-matched controls were genotyped for the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methods. The odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression model. Haplotype frequency was estimated using EH software. RESULTS: The frequency of the MTHFR C677T allele in cases was significantly higher than that in controls (53.5% vs 44.9%, P < 0.001). Compared with the 677CC genotype, the 677CT and 677TT genotypes were associated with increased risk of lung cancer, with the OR being 1.43 (95% CI, 1.04-1.95) and 2.40 (95% CI, 1.61-3.59), respectively. In addition, a significant difference in the distribution of haplotype frequencies between cases and controls was observed. CONCLUSION: Functional polymorphism in MTHFR is associated with increased risk of lung cancer in Chinese population.

Adult↗

PubMed2004

Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer.

Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer development and aggression. Our previous studies revealed a strong association between the MMP-2 -1306C/T polymorphism and risk of several cancers. A novel -735C/T polymorphism in MMP-2 promoter has been identified but the function is undefined. This study examined our hypothesis that these two polymorphisms might have functional relevance and impact on risk of esophageal squamous cell carcinoma in the context of haplotype. Genotypes and haplotypes were analyzed in 527 cases and 777 controls and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The function of the polymorphisms was examined by electrophoretic mobility shift assays, luciferase gene expression assays, and reverse transcriptase-PCR analyses. It was found that the -735C-->T transition disrupts an Sp1 site and displays a lower promoter activity. The C(-1306)-C(-735) haplotype had 7-fold increased luciferase expression and 3.7-fold increased MMP-2 mRNA levels in esophageal tissues compared with the T(-1306)-T(-735) haplotype. A case-control analysis revealed a 1.52-fold (95% CI = 1.17-1.96) or 1.30-fold (95% CI = 1.04-1.63) excess risk of developing esophageal squamous cell carcinoma for the -1306CC or -735CC genotype carriers compared with noncarriers, respectively. A greater association was observed between elevated risk of developing esophageal squamous cell carcinoma and C(-1306) or C(-735) allele containing haplotypes, with the risk being highest for the C(-1306)-C(-735) haplotype compared with the T(-1306)-T(-735) haplotype (OR = 6.53; 95% CI = 2.78-15.33). The C(-1306)-C(-735) haplotype was also associated with increased risk for distant metastasis of esophageal squamous cell carcinoma (OR = 3.34; 95% CI = 1.16-9.63). These findings suggest that the C(-1306)-C(-735) haplotype in the MMP-2 promoter contributes to risk of the occurrence and metastasis of esophageal squamous cell carcinoma by increasing expression of MMP-2.

Alleles↗

PubMed2004

Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma.

Aurora-A/BTAK/STK15, involved in regulating centrosomes and chromosome segregation, is overexpressed in human breast carcinoma and other cancers. The Phe31-->Ile polymorphism in Aurora A alters the kinase function, with the Ile31 variant being preferentially amplified and associated with degree of aneuploidy in human tumors. We have previously shown that the Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal cancer. This case-control study examined the contribution of this polymorphism to susceptibility to development and progression of breast cancer. Aurora A genotypes were determined in 520 patients with breast carcinoma, 191 patients with benign breast diseases (BBD) and 520 controls. It was found that the Aurora A Ile/Ile genotype was significantly associated with increased risk of breast carcinoma occurrence [odds ratio (OR) 1.66; 95% confidence interval (95% CI) 1.29-2.12] compared with the Phe/Phe or Phe/Ile genotype. The increased risk for BBD and breast carcinoma related to the Ile/Ile genotype was more pronounced in younger subjects. Moreover, we found that patients carrying the Ile/Ile genotype tended to have ER-carcinomas (OR 2.56; 95% CI 1.24-5.26). No significant association was observed between the polymorphism and metastasis and disease stage of the cancer. These findings suggest that the Phe31Ile polymorphism in Aurora A may be a genetic modifier for developing breast carcinoma.

Adult↗

PubMed2004

Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma.

BACKGROUND: The FAS receptor-ligand system is a key regulator of apoptotic cell death, and loss of FAS expression and gain of FAS ligand (FASL) expression play important roles in the development and progression of cancer. Single-nucleotide polymorphisms in the promoter region of the FAS (G or A at position -1377 [FAS -1377G/A] and A or G at position -670 [FAS -670A/G]) and FASL (T or C at position -844 [FASL -844T/C]) genes alter the transcriptional activity of these genes. We examined the association between these polymorphisms and risk of the development and metastasis of esophageal squamous-cell carcinoma. METHODS: Genotypes of 588 case patients with esophageal squamous-cell carcinoma and 648 control subjects were determined by polymerase chain reaction-based restriction fragment length polymorphism. Associations with the risk of esophageal squamous-cell carcinoma were estimated by logistic regression. All statistical tests were two-sided. RESULTS: We observed a statistically significantly increased risk of esophageal squamous-cell carcinoma associated with the FAS -1377AA (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.29 to 2.48; P<.001) or FAS -670GG (OR = 1.72, 95% CI = 1.26 to 2.34; P<.001) genotype, which are in strong linkage disequilibrium compared with the FAS -1377GA or GG or the FAS -670AG or AA genotype, respectively. An increased risk of esophageal squamous-cell carcinoma was also associated with the FASL -844CC genotype (OR = 2.06, 95% CI = 1.64 to 2.59; P<.001) compared with the FASL -844CT or TT genotype. Gene-gene interactions of FAS and FASL polymorphisms increased the risk of esophageal squamous-cell carcinoma in a multiplicative manner (OR for the presence of both FAS -1377AA and FASL -844CC genotypes = 4.55, 95% CI = 2.75 to 7.48; P =.001, test for homogeneity). Statistically significant interactions were found between these polymorphisms in FAS and FASL and tobacco smoking. None of the polymorphisms was associated with risk of differentiation or metastasis of esophageal squamous-cell carcinoma at diagnosis. CONCLUSION: Genetic polymorphisms in the death pathway genes FAS and FASL appear to be associated with an increased risk of developing esophageal squamous-cell carcinoma.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Baroreceptor reflex in heart failure.

Congestive heart failure is a syndrome that is usually initiated by a reduction in pump function of the heart, i.e. a decrease in cardiac output. Initially, a reduction in cardiac output leads to unloading of baroreceptor reflex that, in turn, increases heart rate through vago-sympathetic mechanisms and total peripheral resistance via an increase in sympathetic outflow to vascular beds. In this review we are thinking on how baroreceptor reflex plays a role in the abnormal control of the circulation in heart failure. This review and our recent studies suggest that: (1) baroreceptor reflex is blunted in heart failure; (2) central angiotensin II and reactive oxygen species play an important role in blunted baroreceptor reflex; (3) cardiac sympathetic afferent stimulation and chemoreceptor reflex inhibit baroreceptor reflex; and (4) exercise training normalizes abnormal reflexes in the heart failure state.

Angiotensin II↗

PubMed2004

Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma.

The etiology of esophageal squamous cell carcinoma (ESCC) has been shown to be associated with genetic and certain environmental factors that produce DNA damage. Base excision repair (BER) genes are responsible for repair of DNA damage caused by reactive oxygen species and other electrophiles and therefore are good candidate susceptibility genes for ESCC. We first screened eight BER genes for new and potential functional polymorphisms by resequencing 27 DNA samples. We then identified and genotyped for important tagging single nucleotide polymorphisms (SNPs) in a case-control study of 419 patients with newly diagnosed esophageal cancer and 480 healthy controls by frequency matching on age and sex. The association between genotypes and ESCC risk was estimated by unconditional multivariate logistic regression analysis, and stepwise regression procedure was used for constructing the final logistic regression model. We identified 129 SNPs in the eight BER genes, including 18 SNPs that cause amino acid changes. In the final model, 4 SNPs, including 2 in the coding regions (ADPRT Val762Ala and MBD4 Glu346Lys) and others in noncoding regions (LIG3 A3704G and XRCC1 T-77C), remained as significant predictors for the risk of ESCC. The adjusted odd ratios were 1.25 [95% confidence interval (CI) 1.02-1.53] for the ADPRT 762Ala allele, 1.25 (95% CI 1.02-1.53) for the MBD4 346 Lys allele, 0.78 (95% CI 0.63-0.97) for the LIG3 3704G allele, and 1.38 (95% CI 1.01-1.89) for the XRCC1-77C allele. In addition, we observed a significant gene-gene interaction between XRCC1 Gln399Arg and ADPRT Val762Ala. The results suggest that the polymorphisms in five BER genes may be associated with the susceptibility to ESCC in a Chinese population.

ADP Ribose Transferases↗